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Familial breast cancer

  • Chapter
Genetic Predisposition to Cancer

Abstract

Breast cancer has been recognized for over 100 years as having a familial component [1]. More recently, a number of epidemiological investigations have attempted to quantify the risks of breast cancer associated with a positive family history. Attempts have also been made to examine whether the pattern of related individuals with breast cancer are consistent with the effects of a single gene of large effect, shared environmental effects, many genes acting in an additive manner, or most likely, a combination of two or more of these effects. In addition to this statistical and observational evidence for the role of genes in the development of breast cancer, a number of specific genes have been identified as playing a role. Perhaps the most notable of these genes is BRCA1, which was identified through genetic linkage studies and localized to the long arm of chromosome 17 [2]. Because BRCA1 has been extensively studied, it is the subject of a separate chapter (Chapter 15) in this book. However, the BRCA1 gene accounts for, at most, half (and probably less) of all familial breast cancer. In this chapter, we will begin by examining the epidemiological evidence for familial risks in breast cancer, then discuss the results of statistical analyses of breast cancer families for the presence of major genetic effects, and describe specific genes other than BRCA1 which influence breast cancer risk. We will also present evidence that additional genes exist, as yet unmapped, which account for a substantial proportion of familial breast cancer.

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References

  1. Broca, P.P. (1866) Traites des Tumeurs. Asselin, Paris, France.

    Google Scholar 

  2. Hall, J.M., Lee, M.K., Newman, B. et al. (1990) Linkage of early-onset familial breast cancer to chromosome 17q21. Science, 250, 1684–9.

    Article  PubMed  CAS  Google Scholar 

  3. Cannon-Albright, L.A., Bishop, D.T., Goldgar, C. and Skolnick, M.H. (1991) Genetic predisposition to cancer, in Important Advances in Oncology, (eds V.T. DeVita Jr., S. Hellman and S.A. Rosenberg), J.B. Lippincott, Philadelphia, pp. 39–55.

    Google Scholar 

  4. Martynova, R.P. (1936) On the genetics of breast cancer in women. Proc. Maxim-Gorky Res. Inst., 4, 159–73.

    Google Scholar 

  5. Jacobsen, O. (1946) Heredity and Breast Cancer, H.K. Lewis, London.

    Google Scholar 

  6. Penrose, L.S., Mackenzie, J.H. and Karn, M.N. (1948) A genetical study of human mammary cancer. Ann. Eugenics, 14, 234–66.

    Google Scholar 

  7. Smithers, D.W. (1948) Family histories of 459 patients with cancer of the breast. Br. J. Cancer, 2, 163–7.

    Article  PubMed  CAS  Google Scholar 

  8. Woolf, C.M. (1955) Investigations on genetic aspects of carcinoma of the stomach and breast. University of California Publications in Public Health, 2, 265–73.

    CAS  Google Scholar 

  9. Anderson, V.E., Goodman, H.O. and Reed, S.C. (1958) Variables Related to Human Breast Cancer, University of Minnesota Press, Minneapolis.

    Google Scholar 

  10. Macklin, M.T. (1959) Comparison of the number of breast-cancer deaths observed in relatives of breast-cancer patients, and the number expected on the basis of mortality rates. J. Natl Cancer Inst., 22, 927–51.

    PubMed  CAS  Google Scholar 

  11. Murphey, D.P. and Abbey, H. (1959) Cancer in Families. (A study of the relatives of 200 Breast Cancer Probands.) Harvard University Press, Cambridge.

    Google Scholar 

  12. Anderson, D.E. (1971) Some characteristics of familial breast cancer. Cancer, 28, 1500–4.

    Article  PubMed  CAS  Google Scholar 

  13. Anderson, D.E. (1972) A genetic study of human breast cancer. J. Natl Cancer Inst. 48, 1029–34.

    PubMed  CAS  Google Scholar 

  14. Anderson, D.E. (1974) Genetic study of breast cancer: identification of a high risk group. Cancer, 34, 1090–7.

    Article  PubMed  CAS  Google Scholar 

  15. Anderson, D.E. (1976) Genetic predisposition to breast cancer. Rec. Res. Cancer Res., 57, 10–20.

    Google Scholar 

  16. Tulinius, H., Day, N.E. Sigvaldason, H. et al. (1980) A population-based study on familial aggregation of breast cancer in Iceland, taking some other risk factors into account, in Genetic and Environmental Factors in Experimental and Human Cancer, (eds H.V. Gelboin et al.), Japan Scientific Society Press, Japan, pp. 303–12.

    Google Scholar 

  17. Brinton, L.A., Hoover, R.N. and Fraumeni, J.F. (1982) Interaction of familial and hormonal risk factors for breast cancer. J. Natl Cancer Inst., 69, 817–22.

    PubMed  CAS  Google Scholar 

  18. Sattin, R.W., Rubin, G.L., Webster, L.A. et al. (1985) Family history and the risk of breast cancer. JAMA, 253, 1908–13.

    Article  PubMed  CAS  Google Scholar 

  19. Ottman, R., Pike, M.C., King, M-C, Casagrande, J.T. and Henderson, B.E. (1986) Familial breast cancer in a population based series. Am. J. Epidemiol, 123, 15–21.

    PubMed  CAS  Google Scholar 

  20. Negri, E., La Vecchia, C, Bruzzi, P. et al. (1988) Risk factors for breast cancer: pooled results from three Italian case-control studies. Am. J. Epidemiol., 128, 1207–15.

    PubMed  CAS  Google Scholar 

  21. Saftlas, A.F., Wolfe, J.N., Hoover, R.N. et al. (1989) Mammographic parenchymal patterns as indicators of breast cancer risk. Am. J. Epidemiol., 129, 518–26.

    PubMed  CAS  Google Scholar 

  22. Carter, C.L., Jones, D.Y., Schatzkin, A. and Brinton, L.A. (1989) A prospective study of reproductive, familial and socioeconomic risk factors for breast cancer using NHANES I data. Public Health Rep., 104, 45–50.

    PubMed  CAS  Google Scholar 

  23. Schildkraut, J.M., Risch, N. and Thompson, W.D. (1989) Evaluating genetic association among ovarian, breast, and endometrial cancer: evidence for a breast/ovarian cancer relationship. Am. J. Hum. Genet., 45, 521–9.

    PubMed  CAS  Google Scholar 

  24. Mettlin, C, Croghan, I., Natarajan, N. and Lane, W. (1990) The association of age and familial risk in a case-control study of breast cancer. Am. J. Epidemiol., 131, 973–83.

    PubMed  CAS  Google Scholar 

  25. Claus, E.B., Risch, N. and Thompson, W.D. (1990) Age of onset as an indicator of familial risk of breast cancer. Am. J. Epidemiol., 131, 961–72.

    PubMed  CAS  Google Scholar 

  26. Houlston, R.S., McCarter, E., Parbhoo, S. et al. (1992) Family history and risk of breast cancer. J. Med. Genet., 29, 154–7.

    Article  PubMed  CAS  Google Scholar 

  27. Tulinius, H., Egilsson, V., Olafsdottir, G.H. and Sigvaldsson, H. (1992) Risk of prostate, ovarian and endometrial cancer among relatives of women with breast cancer. Br. Med. J., 305, 855–7.

    Article  CAS  Google Scholar 

  28. Slattery, M.L. and Kerber R.A. (1993) A comprehensive evaluation of family history and breast cancer risk. JAMA, 270, 1563–8.

    Article  PubMed  CAS  Google Scholar 

  29. Goldgar, D.E., Easton, D.F., Cannon-Albright, L.A. and Skolnick, M.H. (1994) Systematic population-based assessment of cancer risk in first degree relatives of cancer probands. J. Natl Cancer Inst., 86, 1600–7.

    Article  PubMed  CAS  Google Scholar 

  30. Casagrande, J.T., Hanisch, R., Pike, M.C. et al. (1988) A case-control study of male breast cancer. Cancer Res., 48, 1326–30.

    PubMed  CAS  Google Scholar 

  31. Rosenblatt, K.A., Thomas, D.B., McTiernan, A. et al. (1991) Breast cancer in men: aspects of familial aggregation. J. Natl Cancer Inst., 83, 849–53.

    Article  PubMed  CAS  Google Scholar 

  32. Anderson, D.E. and Badzioch, M.D. (1992) Breast cancer risks in relatives of male breast cancer patients. J. Natl Cancer Inst., 84, 1114–17.

    Article  PubMed  CAS  Google Scholar 

  33. Claus, E.B., Risch, N. and Thompson, W.D. (1991) Genetic analysis of breast cancer in the cancer and steroid hormone study. Am J. Hum. Genet. 48, 232–42.

    PubMed  CAS  Google Scholar 

  34. Claus, E.B., Risch, N. and Thompson, W.D. (1993) Relationship between breast histopathology and family history of breast cancer. Cancer, 71, 147–53.

    Article  PubMed  CAS  Google Scholar 

  35. Erdreich, L.S., Asal, N.R. and Hoge, A.F. (1980) Morphologic types of breast cancer: age, bilaterality, and family history. South. Med. J., 73, 28–32.

    Article  PubMed  CAS  Google Scholar 

  36. Lagios, M.D., Rose, M.E. and Margolin, F.R. (1980) Tubular carcinoma of the breast: association with multicentricity, bilaterality and family history. Am. J. Clin. Pathol., 73, 25–30.

    PubMed  CAS  Google Scholar 

  37. Lagios, M.D. (1977) Multicentricity of breast carcinoma demonstrated by routine correlated serial subgross and radiographic examination. Cancer, 40, 1726–34.

    Article  PubMed  CAS  Google Scholar 

  38. Lynch, H.T., Albano, W.A., Heieck, J.J. et al. (1984) Genetics, biomarkers, and control of breast cancer: a review. Cancer Genet. Cytogenet., 13, 43–92.

    Article  PubMed  CAS  Google Scholar 

  39. Rosen, P.P., Lesser, M.L., Senie, R.T. and Kinne, D.W. (1982) Epidemiology of breast carcinoma. III. Relationship of family history to tumor type. Cancer, 50, 171–9.

    Article  PubMed  CAS  Google Scholar 

  40. Burki, N., Buser, M., Emmons, L.R. et al. (1990) Malignancies in families of women with medullary, tubular, and invasive ductal breast cancer. Eur. J. Cancer Clin. Oncol., 26, 295–303.

    Article  CAS  Google Scholar 

  41. Cannon, L., Bishop, D.T., Skolnick, M.H. et al. (1982) Genetic epidemiology of prostate cancer in the Utah Mormon genealogy. Cancer Surv., 1, 1–12.

    Google Scholar 

  42. Ford, D., Easton, D.F., Bishop, D.T., Narod, S.A., Goldgar D.E. and the BCLC (1994) Risks of cancer in BRCA1-mutation carriers. Lancet, 343, 692–5.

    Article  PubMed  CAS  Google Scholar 

  43. Thompson, W.D. and Schildkraut, J.M. (1991) Family history of gynaecological cancers: relationship to the incidence of breast cancer to age 55. Int. J. Epidemiol., 20, 595–602.

    Article  PubMed  CAS  Google Scholar 

  44. Nelson, C.L., Sellers, T.A., Rich, S.S. et al. (1993) Familial clustering of colon, breast, uterine and ovarian cancers as assessed by family history. Genet. Epidemiol., 10, 235–44.

    Article  PubMed  CAS  Google Scholar 

  45. Anderson, D.E. and Badzioch, M.D. (1993) Familial breast cancer risks: Effects of prostate and other cancers. Cancer, 72, 114–19.

    Article  PubMed  CAS  Google Scholar 

  46. Parazzinni, F., Franceschi, S., Vecchia, C. and Fasoli, M. (1991) The epidemiology of ovarian cancer. Gynecol. Oncol., 43, 9–23.

    Article  Google Scholar 

  47. Lynch, H.T., Guirgis, H.A., Albert, S. et al. (1974) Familial association of carcinoma of the breast and ovary. Surgery, 138, 717–24.

    CAS  Google Scholar 

  48. Bishop, D.T., Albright, L.C., McClellan, T., Gardner, E.J. and Skolnick, M.H. (1988) Segregation and linkage analysis of nine Utah breast cancer pedigrees. Genet. Epidemiol., 5, 151–69.

    Article  PubMed  CAS  Google Scholar 

  49. Bailey-Wilson, J.E., Cannon, L.A. and King, M.-C. (1986) Genetic analysis of human breast cancer: a synthesis of contributions to GAW IV. Genet. Epidemiol. (Suppl), 1, 15–35.

    Article  CAS  Google Scholar 

  50. King, M.-C., Cannon, L.A., Bailey-Wilson, J.E. et al. (1986) Genetic analysis of human breast cancer: literature review and description of family data in workshop. Genet. Epidemiol (Suppl), 1, 3–13.

    CAS  Google Scholar 

  51. Cannon, L.A., Bishop, D.T. and Skolnick, M.H. (1986) Segregation and linkage analysis of breast cancer in the Dutch and Utah families. Genet. Epidemiol., 3(1), 43–6.

    Article  Google Scholar 

  52. King, M.-C, Go, R.C.P., Elston, R.C. et al. (1980) Allele increasing susceptibility to human breast cancer may be linked to the glutamate-pyruvate transaminase locus. Science, 208, 406–8.

    Article  PubMed  CAS  Google Scholar 

  53. Skolnick, M.H., Thompson, E.A., Bishop, D.T. and Cannon, L.A. (1984) Possible linkage of a breast cancer susceptibility locus to the ABO locus: sensitivity of LOD scores to a single new recombinant observation. Genet. Epidemiol., 1, 363–73.

    Article  PubMed  CAS  Google Scholar 

  54. Li, F.P. and Fraumeni, J.F. (1969) Soft tissue sarcomas, breast cancer and other neoplasms: a familial syndrome? Ann. Intern. Med., 71, 747–60.

    Article  PubMed  CAS  Google Scholar 

  55. Birch, J.M., Hartley, A.L., Tricker, K.J. et al. (1994) Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families. Cancer Res., 54, 1298–304.

    PubMed  CAS  Google Scholar 

  56. Borreson, A.L., Anderson, T.I., Garber, J. et al. (1992) Screening for germ line TP 53 mutations in breast cancer patients. Cancer Res., 52, 3234–6.

    Google Scholar 

  57. Sidransky, D., Tokino, T., Helzlsouer, K. et al. (1992) Inherited p53 mutations in breast cancer. Cancer Res., 52, 2984–6.

    PubMed  CAS  Google Scholar 

  58. Swift, M., Reitnauer, P.J., Morrell, D. and Chase, C.L. (1991) Incidence of cancer in 161 families affected by ataxia telangiectasia. N. Engl. J. Med., 325, 1831–6.

    Article  PubMed  CAS  Google Scholar 

  59. Wagner, L.K. (1992) Correspondence: risk of breast cancer in ataxia-telangiectasia. N. Engl J. Med., 326, 1358–9.

    PubMed  CAS  Google Scholar 

  60. Land, C.E. (1992) Correspondence: risk of breast cancer in ataxia-telangiectasia. N. Engl J. Med., 326, 1359–60.

    PubMed  CAS  Google Scholar 

  61. Wooster, R., Ford, D., Mangion, J. et al. (1993) Absence of linkage to the ataxia-telangiectasia locus in familial breast cancer. Hum. Genet., 92, 91–4.

    Article  PubMed  CAS  Google Scholar 

  62. Fuqua, S.A., Chamness, G.C and McGuire, W.L. (1993) Estrogen receptor mutations in breast cancer. J. Cell Biochem., 51, 135–9.

    Article  PubMed  CAS  Google Scholar 

  63. Zuppan, P., Hall, J.M., Lee, M.K., Ponglikit-mongko, M. and King, M.-C. (1991) Possible linkage of the estrogen receptor gene to breast cancer in a family with late-onset disease. Am. J. Hum. Genet., 48, 1065–8.

    PubMed  CAS  Google Scholar 

  64. Krontiris, T.G., Devlin, B., Karp, D.D., Robert, N.J. and Risch, N. (1993) An association between the risk of cancer and mutations in the HRAS1 minisatellite locus. N. Engl. J. Med., 329, 517–23.

    Article  PubMed  CAS  Google Scholar 

  65. Easton, D.F., Bishop, D.T., Ford, D. and Crockford, G.P. (1993) Genetic linkage analysis in familial breast and ovarian cancer — Results from 214 families. Am. J. Hum. Genet., 52, 678–701.

    PubMed  CAS  Google Scholar 

  66. Narod, S.A., Ford D., Devilee P. et al. (1995) An evaluation of genetic heterogeneity in 145 breast-ovarian cancer families. Am. J. Hum. Genet. 56, 2254–64.

    Google Scholar 

  67. Stratton, M.R., Ford, D., Seal, S. et al. (1994) Familial male breast cancer is not linked to the BRCA1 locus on chromosome 17q. Nature Genet., 7, 103–7.

    Article  PubMed  CAS  Google Scholar 

  68. Wooster, R., Neuhausen, S., Mangion, J. et al. (1994) Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science, 265, 2088–90.

    Article  PubMed  CAS  Google Scholar 

  69. Wooster, R., Bignell, G., Swift, S. et al. (1995) Identification of the BRCA2 gene. Nature, 378, 789–92.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. David E. Goldgar
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  2. Michael R. Stratton
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  3. Rosalind A. Eeles
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Editor information

Editors and Affiliations

  1. Cancer Genetics and Clinical Oncology, Institute of Cancer Research and Royal Marsden Hospital, Surrey, UK

    Rosalind A. Eeles (Senior Lecturer and Honorary Consultant) (Senior Lecturer and Honorary Consultant)

  2. CRC Human Cancer Genetics Research Group, University of Cambridge, UK

    Bruce A. J. Ponder (Director) (Director)

  3. CRC Genetic Epidemiology Unit, University of Cambridge, UK

    Douglas F. Easton (Director) (Director)

  4. Academic Unit of Radiotherapy and Oncology, Institute of Cancer Research and Royal Marsden Hospital, Surrey, UK

    Alan Horwich (Director of Clinical Research) (Director of Clinical Research)

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© 1996 Springer Science+Business Media Dordrecht

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Goldgar, D.E., Stratton, M.R., Eeles, R.A. (1996). Familial breast cancer. In: Eeles, R.A., Ponder, B.A.J., Easton, D.F., Horwich, A. (eds) Genetic Predisposition to Cancer. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-4501-3_14

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  • DOI: https://doi.org/10.1007/978-1-4899-4501-3_14

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-412-56580-9

  • Online ISBN: 978-1-4899-4501-3

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